Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
EBAG9 controls CD8+ T cell memory formation responding to tumor challenge in mice
Armin Rehm, … , Gerald Willimsky, Uta E. Höpken
Armin Rehm, … , Gerald Willimsky, Uta E. Höpken
Published April 28, 2022
Citation Information: JCI Insight. 2022;7(11):e155534. https://doi.org/10.1172/jci.insight.155534.
View: Text | PDF
Research Article Immunology Oncology

EBAG9 controls CD8+ T cell memory formation responding to tumor challenge in mice

  • Text
  • PDF
Abstract

Insight into processes that determine CD8+ T cell memory formation has been obtained from infection models. These models are biased toward an inflammatory milieu and often use high-avidity CD8+ T cells in adoptive-transfer procedures. It is unclear whether these conditions mimic the differentiation processes of an endogenous repertoire that proceed upon noninflammatory conditions prevailing in premalignant tumor lesions. We examined the role of cytolytic capacity on CD8+ T cell fate decisions when primed by tumor cells or by minor histocompatibility antigen–mismatched leukocytes. CD8+ memory commitment was analyzed in Ebag9-deficient mice that exhibited enhanced tumor cell lysis. This property endowed Ebag9–/– mice with extended control of Tcl-1 oncogene–induced chronic lymphocytic leukemia progression. In Ebag9–/– mice, an expanded memory population was obtained for anti-HY and anti–SV-40 T antigen–specific T cells, despite unchanged effector frequencies in the primary response. By comparing the single-cell transcriptomes of CD8+ T cells responding to tumor cell vaccination, we found differential distribution of subpopulations between Ebag9+/+ and Ebag9–/– T cells. In Ebag9–/– cells, these larger clusters contained genes encoding transcription factors regulating memory cell differentiation and anti-apoptotic gene functions. Our findings link EBAG9-controlled cytolytic activity and the commitment to the CD8+ memory lineage.

Authors

Armin Rehm, Anthea Wirges, Dana Hoser, Cornelius Fischer, Stefanie Herda, Kerstin Gerlach, Sascha Sauer, Gerald Willimsky, Uta E. Höpken

×

Figure 7

Key genes associated with memory commitment and survival are upregulated in TAg-specific CD8+ T cells from Ebag9–/– mice.

Options: View larger image (or click on image) Download as PowerPoint
Key genes associated with memory commitment and survival are upregulated...
Dot plot representing the size-coded percentage of cells expressing selected genes involved in the differentiation of CD8+ T cells for WT and Ebag9–/– cells among all clusters. Expression changes are depicted according to the color scale. Gene names with the most differential expression between WT and Ebag9–/– cells are depicted in red. The ranges of the cell numbers are represented by the diameter of the circles; each column represents 1 cluster. pct. exp, percentage expression.

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts